The ability of papaya mosaic virus (PapMV) virus-like particles (VLPs) to enhance the immunogenicity of antigens has been described in the following patent and patent applications.
U.S. Pat. No. 7,641,896, Canadian Patent Application No. 2,434,000, and International Patent Application No. PCT/CA03/00985 (WO 2004/004761) describe the use of PapMV or VLPs derived from PapMV coat protein for potentiating an immune response to an antigen in an animal. The antigen(s) may be attached to the PapMV or VLP or they may be administered in combination with the PapMV or VLP.
International Patent Application No. PCT/CA2007/002069 (WO 2008/058396) describes influenza vaccines based on PapMV and PapMV VLPs. The vaccines comprise PapMV or a PapMV VLP and one or more influenza antigens, which may be attached to the PapMV or VLP or may be administered in combination with the PapMV or VLP.
International Patent Application No. PCT/CA2007/001904 (WO 2008/058369) describes immunogenic affinity-conjugated antigen systems based on PapMV. This application describes fusions of PapMV coat protein with a plurality of affinity peptides capable of binding an antigen of interest.
International Patent Application No. PCT/CA2008/000154 (WO 2008/089569) describes vaccines against S. typhi and other enterobacterial pathogens based on PapMV. The vaccines comprise PapMV or a PapMV VLP and one or more enterobacterial antigens, which may be attached to the PapMV or VLP or may be administered in combination with the PapMV or VLP.
International Patent Application No. PCT/CA2009/00636 (WO 2010/012069) describes multivalent vaccines that comprise a PapMV component and one or more antigens, and their use to provide protection against a plurality of strains of a pathogen, or against more than one pathogen. The vaccines can optionally comprise a Salmonella spp. porin component.
The preparation of PapMV VLPs from isolated PapMV coat protein has been described. Erickson and Bancroft (1978, Virology, 90:36-46 & 1978, Virology, 90:47-53) first described the preparation of PapMV VLPs by in vitro self-assembly of isolated PapMV coat protein and PapMV RNA. The PapMV coat protein preparation used in these experiments was isolated from PapMV and was dominated by polymeric forms of the protein (sedimenting at 3 S, 14 S and 25 S), one or more of which were believed to be essential for initiation of VLP formation. Subsequent studies by Sit, et al. (1994, Virology, 199:238-242) established that the first 38-47 nucleotides of the PapMV genome were required for initiation of assembly and proposed that the initiation complex also required the 14 S polymer species.
It was later demonstrated that PapMV VLPs could be prepared from a monomeric form of the PapMV coat protein expressed in E. coli. The recombinant coat protein self-assembled within the bacterial cells and VLPs could be isolated by rupture of the cells, followed by several purification steps, including detergent treatment (see Tremblay et al. 2006, FEBS J., 273:14-25; International Patent Application Nos. PCT/CA2007/002069 (WO 2008/058396), PCT/CA2007/001904 (WO 2008/058369), PCT/CA2008/000154 (WO 2008/089569) and PCT/CA2009/00636 (WO 2010/012069)).
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.